Point-of-care assays for hemoglobin A(1c): is performance adequate?

The routine measurement of hemoglobin A1c (Hb A1c) 1 has become an essential component of the standard of care for patients with diabetes and has been recommended by major clinical diabetes organizations. A small amount of evidence shows that having the Hb A1c result at the time of the doctor’s visit is beneficial (1 ). Recently, there has been discussion about whether the quality of point-ofcare (POC) testing for Hb A1c is sufficient to meet clinical needs (2). The National Glycohemoglobin Standardization Program (NGSP) certifies methods annually at the manufacturer level, with only 1 lot of reagents being used at any point in time. Although College of American Pathologists proficiency testing provides an excellent snapshot of the performance of each method in the clinical laboratory, POC methods are CLIA waived; thus, users are not required to participate in proficiency testing. Inadequate performance of some of these methods in the hands of experienced users (2) has raised concerns about the ability of these methods to perform well enough for diabetes monitoring. The manufacturer of the A1cNow device (Bayer HealthCare) noted (3) that the use of EDTAcontaining blood in the previous study (2) was not in accordance with manufacturer recommendations. The manufacturers of Afinion (AxisShield) and in2it (Bio-Rad Laboratories) purportedly have made improvements to these methods since the original evaluation; therefore, we reexamined the Afinion, A1cNow (using heparinized blood), and in2it methods in this study. Two lots of A1cNow and Afinion reagents were shipped to each of 2 NGSP secondary reference laboratories (SRLs), one in the US (laboratory A) and the other in Europe (laboratory B) for a total of 4 reagent lots tested for each method. Two lots of the in2it reagents were shipped to one of the laboratories (laboratory B). For each method, each lot was evaluated according to CLSI EP-5 guidelines for imprecision with whole blood and/or manufacturer QC material. All evaluations for the A1cNow device were performed with heparin-anticoagulated whole blood. EDTA-anticoagulated whole blood was used for both the Afinion and in2it evaluations. Each lot was compared with an NGSP SRL method, as would be done for NGSP method certification, with Bland– Altman assessment of agreement with current NGSP manufacturer certification limits (4, 5). For the A1cNow and Afinion methods, a likelihood ratio test was used to evaluate for statistically significant differences in results among reagent lots between and within laboratories. For the in2it method, 2 reagent lots were evaluated in a single laboratory; therefore, an overall test of coincidence of the least squares regression lines was used to test for a statistically significant difference between the lots. For all tests, a P value 0.05 was considered to indicate statistical significance. Total CVs were between 3.4% and 5.1% for the A1cNow method (Table 1), whereas CVs were lower